Potassium Carbonate → Linagliptin

Participants

Reaction Conditions

Reaction Steps

1-[(4-Methyl-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-bromoxanthine (20 gm) and methyl isobutyl ketone (MIBK 200 mL) were charged into a 1000 mL round bottomed flask equipped with a mechanical stirrer. Potassium carbonate (18.3 gm) and (R)-piperidine-3-amine dihydrochloride (8.4 gm) were added to the reaction mixture at 26° C. The reaction mixture was heated to 100° C. and maintained at that temperature for 4 hours. The reaction mixture was cooled to 30° C. and filtered and washed with MIBK (40 mL). The filtrate was charged into another flask and added 200 mL of 10% aqueous acetic acid solution and stirred for 30 minutes at 28° C. The aqueous layer was separated and washed with 60 mL of dichloromethane. The aqueous layer was charged into another flask and 200 mL of dichloromethane and 100 mL of aqueous sodium hydroxide solution (16 gm of sodium hydroxide in 100 mL of water) were added drop-wise at 28° C. (pH is ≧10). The mixture was stirred for one hour at 28° C. and the organic layer was separated and the aqueous layer was extracted with 100 ml of dichloromethane. Combined the organic layers and divided into 5 equal parts.

Provenance & Evidence